Is ABCA1 p.Thr609= (c.1827G>A) pathogenic?

ABCA1 p.Thr609= (c.1827G>A) is classified Conflicting classifications of pathogenicity in ABCA1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-22). Ultra-rare (popmax 0.01%, amr); Associated with Tangier disease.

What condition is associated with ABCA1 p.Thr609= (c.1827G>A)?

ABCA1 p.Thr609= (c.1827G>A) is associated with Tangier disease, hypoalphalipoproteinemia, primary, 1 (ClinVar).

How common is ABCA1 p.Thr609= (c.1827G>A) in the general population?

ABCA1 p.Thr609= (c.1827G>A) is ultra-rare (popmax 0.01%, amr) (gnomAD).

How is Tangier disease inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ABCA1 p.Thr609=

c.1827G>A · rs1454126964 · VCV913347

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Conditions

Tangier disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -4.2
Overall
CADD	0.198	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,986 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00062% 10/1,613,822 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,998
South Asian	0.0011%	91,058
European (non-Finnish)	0.000254%	393,335

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ABCA1
Protein: p.Thr609=
Coding: c.1827G>A
MANE Select: NM_005502
dbSNP: rs1454126964
Type: single nucleotide variant
Location: chr9:104830990 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB

Full ABCA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Tangier disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypoalphalipoproteinemia, primary, 1

For Tangier disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal

Similar variants

ABCA1 p.Thr609fs Pathogenic same residue
ABCA1 p.Thr609Met Uncertain significance ★ ⚠ same residue
ABCA1 c.5237+3A>C Likely pathogenic ★★ same condition
ABCA1 p.Arg2080Trp Likely pathogenic ★★ same condition
ABCA1 p.Arg587Trp Pathogenic/Likely pathogenic ★★ same condition
ABCA1 p.Asn1800His Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCA1 c.*2330A>T Uncertain significance ★★ same condition
ABCA1 c.*379C>T Uncertain significance ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abca1-p-thr609 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown